This project represents continuing collaboration between clinical and basic scientists to characterize the biophysical forces acting on arterial lesions. The modeling tools have been developed to the point where they can characterize the biophysical forces acting on giant cerebral fusiform aneurysms. Left untreated, giant aneurysms can continue to enlarge over the life of the patient. The risk of death or devastating morbidity approaches 85% over 5 years. To slow growth, the feeding artery is often occluded in the hope that it decreases hemodynamic stress. However, because local wall shear stress and pressure cannot be measured directly, quantitative data is lacking. We will test the primary hypothesis that treatments that decrease shear stress and pressure on the aneurysm wall slows the growth of giant aneurysms. Theoretical predictions of altered hemodynamics will be correlated to experimental values. The methods will include theoretical computational modeling, based on experimental characterization of the aneurysm by MRA, velocity encoded MRI, and CT. Computational patient-specific models will be developed from measured geometry and inlet flow. Data will be retrieved from 15 consecutive patients (5/year) to quantify vascular structure and hemodynamics. About half of the patients will be treated by proximal artery occlusion and half left untreated at the discretion of the surgeon, based on best clinical practices. Aim I: Validating computational model assessment of velocity from MRI data: Aneurysm geometry and inlet flow derived from in vivo imaging prior to intervention will be reproduced in three representative physical models, and the velocity field will be measured and compared to simulations. We hypothesize that the velocity predicted by simulation will be in agreement with measurements in the physical model. Aim II: Theoretical prediction of changes in shear stress and pressure due to treatment: To stimulate aneurysms that had undergone surgical treatment, patient- specific computational models will be modified by simulating occlusion in a proximal feeding artery. The predicted change in flow will be correlated to the change in flow measured by MRI. Aim II: Associating aneurysms growth to biophysical forces: Shear stress and pressure estimated in untreated and treated aneurysms will be compared to measured aneurysm growth. We hypothesize that a change in aneurysm volume will be directly correlated with shear stress and pressure on the wall. The significance of the work is that patient-specific models can predict the result of surgical intervention, and provide clinicians with the ability evaluate emerging methods to treat aneurysms (e.g., stents, coiling).